Researchers call for more studies to determine threshold for intervention.

There is a consistent, graded linear association between glucose levels in pregnant women and adverse clinical outcomes, according to a meta-analysis published in The British Medical Journal. The investigation, which included 23 published clinical studies involving more than 200,000 women, concluded that there is no clear threshold at which the risk of adverse perinatal events occurs in pregnant women with gestational diabetes. The findings suggest that “decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary,” according to the authors.

The researchers, from the United Kingdom (UK) and Ireland, conducted the analysis to identify the optimal oral glucose tolerance testing (OGTT) threshold that should define gestational diabetes. Current thresholds from the International Association of Diabetes and Pregnancy Study Groups (IADPSG) rely on data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. That study showed graded linear increases in large for gestational age (LGA), large skinfold thicknesses, and high cord blood C peptide, as well as other adverse perinatal outcomes, across the entire distribution of fasting and post-load glucose in women without existing diabetes or gestational diabetes.

Thus, the IADPSG calculated thresholds as the glucose values at which the odds for birthweight, cord C peptide, and percent body fat above the 90th centile reached 1.75 times the estimated odds of these outcomes above mean glucose values.

While the World Health Organization and the International Federation of Gynecology and Obstetrics endorse the criteria, the UK’s National Institute of Health and Care Excellence and the American College of Obstetrics and Gynecology do not. In addition, the authors of the BMJ study note, the HAPO study did not present results by country. This could be a problem, they wrote, because the “shape and magnitude of the association between glycemia and pregnancy outcomes could differ in different populations.”

For their analysis, the researchers extracted glucose test results for an oral glucose challenge test (OGCT)(50 g) and OGTT (75 g and 100 g) at fasting and 1- and 2-hour post-load timings.

They found positive linear associations with cesarean section, induction of labor, LGA, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations with no clear evidence of a threshold effect. They also found generally stronger associations for fasting than for post-load concentrations.

The findings, the authors wrote, have “resource implications for maternity services in terms of antenatal care (OGTTs, treatments, induction of labor), intrapartum care (caesarean section), and short and longer term postnatal care (infant care, screening for type 2 diabetes).”

Lowering the glucose thresholds currently used to diagnose gestational diabetes in pregnant women could reduce the risk of adverse outcomes and their associated costs, they suggested. However, the researchers added, there are currently no trials using the thresholds, or “robust evidence that the longer-term risk of obesity would be improved.”

Thus, the investigators called for future research that combines their results with “robust evidence from well-conducted randomized trials (and meta-analyses of those) of treatment effects on adverse outcomes related to gestational diabetes.”